Histopathologic parameters in the evaluation of T1 squamous cell carcinomas of the oral cavity

BACKGROUND: Prognostic indicators that could assist in a more precise selection of patients with small oral carcinomas for differentiated therapy would be valuable. A significant fraction of patients with stage I disease have a relatively poor prognosis despite the small size of the tumor, but in general stage I tumors of the oral cavity have a favorable prognosis. METHODS: Seventy-eight patients with stage I (T1N0M0) oral squamous cell carcinoma from two different ENT departments were included in the study. The pretreatment biopsy specimens were graded according to the modified classification of Jakobsson et al. Eight individual parameters were recorded, four parameters describing the tumor cell population and four parameters describing the tumor/host interaction. RESULTS: The only significant prognostic parameter for disease-specific survival was "mode of invasion." The histologic mean score was not significantly correlated to disease-specific or crude survival. CONCLUSIONS: Mode of invasion is the most important histologic parameter when evaluating the prognosis. Histologic evaluation of small squamous cell carcinomas of the oral cavity may assist the design of a differentiated treatment strategy (eg, monotherapy vs combined treatment).     

Pattern of nonspecific (or global) DNA methylation in oral carcinogenesis

BACKGROUND: Although alterations in nonspecific (or global) DNA methylation (GDM) in specific cells are known to be involved in the process of lung carcinogenesis, similar associations have not been evaluated in other smoking-related cancers of the head and neck. METHODS: We evaluated the status of GDM by using monoclonal antibodies specific for 5-methylcytosine (5-mc) in oral squamous cell carcinoma (SCC) specimens of 48 cigarette smokers who had SCC develop and in 93 age-, race-, and sex-matched smokers who did not. RESULTS: Percentages of cells positive for 5-mc immunostaining of DNA of SCC and dysplastic lesions were significantly higher than those of normal oral epithelial cells from cancer subjects and from noncancer subjects. The degree of DNA methylation was unrelated to DNA content. CONCLUSIONS: The pattern of GDM in oral SCCs is different from that of lung SCCs. The differences in nutrient risk factor profiles that are related to GDM and differential activity of DNA methyltranferases between oral and lung SCCs may explain these observations.     

Resection margins in oral cancer surgery: Room for improvement

The purpose of this review was to identify publications on resection margins in oral cancer surgery and compare these with the results from 2 Dutch academic medical centers. Eight publications were considered relevant for this study, reporting 30% to 65% inadequate resection margins (ie, positive and close margins), compared to 85% in Dutch centers. However, clinical outcome in terms of overall survival and recurrence seemed comparable. The misleading difference is caused by lack of unanimous margin definition and differences in surgicopathological approaches. This prevents comparison between the centers. Data from Dutch centers showed that inadequate resection margins have a significantly negative effect on local recurrence, regional recurrence, distant metastasis, and overall survival. These results confirm the need for improvement in oral cancer surgery. We underline the need for consistent protocols and optimization of frozen section procedures. We comment on development of optical techniques for intraoperative assessment of resection margins. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2197–E2203, 2016     

Utility of toluidine blue in oral premalignant lesions and squamous cell carcinoma: continuing research and implications for clinical practice

Toluidine blue (TB) has been shown to aid in the detection and diagnosis of oropharyngeal squamous cell carcinoma (OSCC) and oral premalignant lesions (OPLs). TB has been shown to enhance visualization of oral lesions and assist in identifying sites of increased risk of dysplastic/malignant change and promote biopsy. TB has been shown to identify lesions with molecular changes associated with risk of progression of OPLs to OSCC. A recent prospective longitudinal study showed TB retention in histologic benign lesions and lesions with mild dysplasia that are at increased risk of progression to cancer. Clinical trials show that TB is useful in identifying asymptomatic OSCC and premalignant lesions at risk of progressing to SCC, which might otherwise be undetected until lesions become more advanced. The data supports TB use in oral examination of patients at risk of OSCC.     

Exploring the link between microorganisms and oral cancer: A systematic review of the literature

The majority of cases of oral cancer have been related to tobacco use and heavy alcohol consumption. However, the incidence of oral cavity carcinoma appears to be increasing in many parts of the world in a manner that it is difficult to explain with traditional risk factors alone. Meanwhile, interest in the possible relationships between microorganisms and the different stages of cancer development has been rising and numerous mechanisms by which bacteria and yeast may initiate or promote carcinogenesis are currently under investigation. In particular, a persuasive body of evidence suggests a possible etiological role involving the metabolism and production of carcinogenic products, such as acetaldehyde. Other suggested mechanisms include the induction of chronic inflammation and direct interference with eukaryotic cell cycle and signaling pathways. This review aims to summarize the known associations between microbial infection and cancer and draw attention to how they may relate to oral carcinoma. © 2009 Wiley Periodicals, Inc. Head Neck, 2009     

Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report

BACKGROUND: Oral cancer has been identified as a significant public health threat. Systematic evaluation of the impact of this disease on the US population is of great importance to health care providers and policy makers. METHODS: This study used the National Cancer Data Base (NCDB) to evaluate associations between demographic and disease characteristics, treatment, and survival for patients with oral cavity cancer in the United States. Of patients diagnosed between 1985 and 1996, 58,976 were extracted from the NCDB. ANOVAs were performed on selected cross-tabulations, and relative survival was used to calculate outcome. RESULTS: Median age of patients was 64.0 years. Men made up 60.2% of patients. Pathologic diagnosis was squamous cell carcinoma (SCC) in 86.3% of cases. Younger patients had a much higher frequency of non-SCC, and this was related to survival in these patients. African-Americans (independent of income), lower income patients, and patients with higher grade disease were seen more frequently with advanced-stage SCC. Five-year relative survival for SCC cases was lower for older patients, men, and African-Americans. CONCLUSIONS: This study addressed many issues related to oral cancer that have been previously discussed in the literature. The demographic, site, stage, histologic, and survival data available for this large number of cases in the NCDB allowed an accurate characterization of the contemporary status of oral cancer in the United States.     

Tumor thickness influences prognosis of T1 and T2 oral cavity cancer—but what thickness?

BACKGROUND: Previous studies have demonstrated that tumor thickness might influence prognosis in oral cancer, but the significant point at which outcome changes has varied from 1.5 mm to 6 mm. The clinical relevance of thickness remains unclear, and a reproducible prognostic "breakpoint" needs to be defined. METHODS: Tumor thickness was measured in 145 oral cavity squamous cancers, clinically staged T1 (n = 62) or T2 (n = 83). Clinical and pathologic data were collected prospectively between 1988 and 2000, but thickness was measured on paraffin sections for this study. Minimum follow-up was 2 years, and thickness was correlated with local control, cervical node involvement, and survival. Patients with clinically positive nodes (n = 21) were not excluded. Overall, 55 patients had pathologic node involvement at some time in their disease. RESULTS: Median tumor thickness was 6.2 mm, and there was little variation between sites: tongue, 6.4 mm; floor of mouth, 6.6 mm; and other sites, 5.7 mm. Median thickness for T1 tumors was 4.3 mm, significantly less than the T2 group, 8 mm (p <.01). Median thickness also varied significantly for tumors with associated nodal disease (8.5 mm) and without nodal disease (5.8 mm) (p <.01). Prognosis changed significantly at a cutoff of 4 mm with local control, nodal disease, and survival rates of 91%, 8%, and 100%, respectively, for tumors <4 mm compared with 84%, 48%, and 74% for those 4 mm or more thick (p <.01). Subgrouping greater than and less than 3 mm and 5 mm also showed a difference but with poorer discrimination. Thickness and pathologic nodal involvement were highly significant independent prognostic factors. CONCLUSIONS: Tumor thickness is a highly significant, objectively measurable prognostic factor in early stage oral cancers. There is a need to standardize techniques of measurement to allow a multi-institutional study to be carried out. This will facilitate the development of strategies aimed at improving the outcome of higher risk patients.